Antioxidant effects of propofol in human hepatic microsomes: Concentration effects and clinical relevance

Abstract

Propofol is known to possess antioxidant properties. There is controversy regarding the mechanisms by which the drug produces its antioxidant effects and the significance of these effects in relation to plasma concentrations of propofol in clinical practice. We studied the effects of increasing concentrations of Intralipid, propofol, butylated hydroxytoluene (BHT) and a vitamin E analogue (Trolox C) in 0.9% saline on non-enzymic and enzymic lipid peroxidation in human hepatic microsomes, and on concentrations of antioxidant enzymes in a Hep G2 cell line. Propofol showed significant inhibition of lipid peroxidation, but was less potent than BHT or Trolox C. IC50 values for non-enzymic and enzymic lipid peroxidation were mean 9.47 (SD 0.86) and 7.39 (0.84) μmol litre-1 for propofol, 1.30 (0.57) and 0.32 (0.02) μmol litre-1 for BHT and 2.34 (0.68) and 0.35 (0.04) μmol litre-1 for Trolox C, respectively. The antioxidant activities of propofol were substantially retained in the presence of up to 30 g litre-1 of human serum albumin. Propofol at concentrations of up to 100 μmol litre-1 had no significant effect on the activities of antioxidant enzymes. Clinically relevant concentrations of propofol produced significant inhibition of both enzymic and non-enzymic lipid peroxidation in hepatic microsomal preparations, possibly as a result of accumulation in lipophilic environments. Measurement of antioxidant effects of drugs in aqueous media may have little relevance to their effects in protecting against lipid peroxidation in biological systems.